In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 51, No. 9 ( 2007-09), p. 3304-3310
Abstract:
Beta-lactams are regularly administered in intermittent short-term infusions. The percentage of the dosing interval during which free drug concentrations exceed the MIC ( fT 〉 MIC ) is the measure of drug exposure that best correlates with clinical outcome for beta-lactams. Therefore, administration by continuous infusion has gained increasing interest recently. We studied 20 critically ill patients with nosocomial pneumonia and investigated whether continuous infusion with a reduced total dose, compared to the standard regimen of intermittent short-term infusion, results in a superior probability of target attainment as assessed by the fT 〉 MIC value of imipenem. In this prospective, randomized, controlled clinical study, patients received either a loading dose of 1 g/1 g imipenem and cilastatin (as a short-term infusion) at time zero, followed by 2 g/2 g imipenem-cilastatin per 24 h as a continuous infusion for 3 days ( n = 10), or 1 g/1 g imipenem-cilastatin three times per day as a short-term infusion for 3 days (total daily dose, 3 g/3 g; n = 10). Imipenem concentrations in plasma were determined by using a validated liquid chromatography-tandem mass spectrometry assay. A two-compartment open model was employed for population pharmacokinetic modeling. We simulated 10,000 intensive-care-unit patients via Monte Carlo simulations for pharmacodynamic evaluation using the target 40% fT 〉 MIC . The probability of target attainment by MIC for intermittent infusion was robust ( 〉 90%) up to MICs of 1 to 2 mg/liter. The corresponding value for continuous infusion was 2 to 4 mg/liter. Although all 20 patients had an fT 〉 MIC of 100%, 3 patients died. Patient survival was best described by employing a sepsis-related organ failure assessment score as a covariate in a logistic regression analysis. Larger clinical trials are warranted for evaluation of continuous infusions at a reduced dose of imipenem for critically ill patients.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.01318-06
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2007
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
Permalink
